Yusuke Shono, MD, PhD

Hokkaido University Graduate School of Medicine, Sapporo, Japan; Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become widely applied for hematological (and more recently even for non-hematological) disorders. However, allo-HSCT is a “two-edeged” swords; this treatment has preferable strong graft-versus-tumor effects (GVT) to cure diseases while at the same time this causes graft-versus-host disease (GVHD) that could lead to the adverse prognoses of treated patients. As a hematologist I observed many of the complications including GVHD after allo-HSCT, and also as a researcher I elucidated the effects of GVHD on hematopoiesis/hematopoietic niche, I keep on pursuing my research in this field of transplantation immunology trying to reveal the detailed mechanisms of GVHD and GVT. After joining in the lab since April 2011, I have been focusing attention on a network hub controlling immunity, inflammation, and cancer - especially a transcriptional factor c-Rel that controls T-cell activation and proliferation contributing to pathophysiology of GVHD/GVT. We have small molecule c-Rel inhibitor compounds in our hands and by utilizing these compounds in vivo and in vitro, we observed effective suppression of c-Rel resulting in improved GVHD while preserving GVT activity. Intestinal damages are also important to initiate/sustain GVHD, so my projects also include models using knock-out mice of specific genes relevant to intestinal immune homeostasis. In addition, I am also involved in the project focusing on mucosal immunology and examine how it can impact on intestinal GVHD, including the microbial flora and dietary factors. The ultimate goal is to develop promising methods to improve clinical outcomes of allo-HSCT.